Donor-Specific HLA Antibodies: Risk Factors and Outcomes After Kidney Transplantation

Berga, J. Kanter; Mateu, L.M. Pallardó; Catalán, Sandra Beltrán; Alcaraz, N. Puig; Calabuig, Asunción Sancho; Martínez, Eva Gavela; Bernabeu, A. Ávila; Albiach, J. Crespo

doi:10.1016/j.transproceed.2011.06.053

Cited by 17 publications

(9 citation statements)

References 14 publications

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“… 6 , 42 , 47 - 49 This may result from a more robust immune system or may simply be a consequence of greater nonadherence. African American race, 43 male sex, 48 the pre-existence of non-DSA HLA at the time of transplantation, and persistent BK virus infection 50 also appear to influence risk. Other important factors include sensitization events, such as retransplantation, 47 , 51 pregnancy, 52 and blood transfusions 51 , 53 or indicators of high immunological risk, such as previous acute rejection.…”

Section: Immunosuppression-independent Risk Factors For Dndsa Productmentioning

confidence: 99%

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The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

et al. 2016

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Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.

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Section: Immunosuppression-independent Risk Factors For Dndsa Productmentioning

confidence: 99%

“…Other important factors include sensitization events, such as retransplantation, 47 , 51 pregnancy, 52 and blood transfusions 51 , 53 or indicators of high immunological risk, such as previous acute rejection. 4 , 41 , 47 , 48 , 54 , 55…”

Section: Immunosuppression-independent Risk Factors For Dndsa Productmentioning

confidence: 99%

The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

et al. 2016

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“…Many studies have revealed that younger age at LT is associated with DSA development, 7 , 13 , 15 , 16 , 21 and our previous studies indicated that patients who underwent LDLT when they were younger than 3 years had higher rate of DSA. 10 Univariate analysis in the present study also showed the association between younger age at LT and DSA development.…”

Section: Discussionmentioning

confidence: 82%

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability

Tokodai

Miyagi

Nakanishi

et al. 2017

Transplantation Direct

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BackgroundIn pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression.MethodsWe retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013. Patients were divided into 2 groups based on the CNI trough level. The cutoff trough levels were 3 and 30 ng/mL for tacrolimus and cyclosporine, respectively. Luminex single-antigen bead assays were performed, and the cutoff for a positive reaction was set at a mean fluorescence intensity (MFI) of at least 1000.ResultsThe mean recipient ages at the time of LT were 29.1 and 77.2 months for the low and regular CNI groups, respectively (P = 0.0007). Univariate logistic regression analysis revealed that recipient age at LT younger than 3 years (P = 0.0099) and low CNI (P < 0.0001) were significantly associated with DSA development. In multivariate analysis, low CNI was an independent risk factor of DSA development (P = 0.0011). Of 15 high-MFI DSAs, 3 were anti-DR, and 12 were anti-DQ. Two of 3 anti-DR DSAs and 11 of 12 anti-DQ DSAs had complement-binding ability and high MFIs.ConclusionsCNI minimization was an independent risk factor for posttransplant DSA during long-term follow-up after pediatric LT. Adjusting CNI to appropriate levels is a safe first step to prevent the immunological effects of DSA.

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“…Furthermore, the decrease of sCD30 after transplantation was associated in our patients with the use of anti-CD25 antibodies. Most patients in the study (80%) received induction therapy; hence, they were at lower risk for AR [45]. Nevertheless, we suggest that further investigations are necessary to evaluate the predictive value of posttransplant sCD30.…”

Section: Discussionmentioning

confidence: 99%

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients’ Survival

Trailin

Ostapenko²,

Nykonenko

et al. 2017

Disease Markers

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Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

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Donor-Specific HLA Antibodies: Risk Factors and Outcomes After Kidney Transplantation

Cited by 17 publications

References 14 publications

The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients’ Survival

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